rs201957861
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152743.4(BRAT1):āc.770A>Cā(p.His257Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,526,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_152743.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAT1 | NM_152743.4 | c.770A>C | p.His257Pro | missense_variant | 5/14 | ENST00000340611.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAT1 | ENST00000340611.9 | c.770A>C | p.His257Pro | missense_variant | 5/14 | 1 | NM_152743.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151840Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000264 AC: 5AN: 189680Hom.: 0 AF XY: 0.0000394 AC XY: 4AN XY: 101472
GnomAD4 exome AF: 0.0000145 AC: 20AN: 1375084Hom.: 0 Cov.: 33 AF XY: 0.0000178 AC XY: 12AN XY: 673752
GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151840Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74130
ClinVar
Submissions by phenotype
Neonatal-onset encephalopathy with rigidity and seizures Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 13, 2022 | This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 257 of the BRAT1 protein (p.His257Pro). This variant is present in population databases (rs201957861, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with BRAT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 540158). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at